Much of the research assessing the placental transport of drugs of abuse and potentially harmful effects of prenatal exposure and, and particularly the mechanisms of such effects, is performed in animals. This contract specifically deals with the development of an in vitro cell culture model for the placental barrier. This will be used to screen the placental permeability and metabolism of the drugs of abuse. Some of the advantages of an in vitro cell culture model is that it provides a preliminary drug screening mechanism that is fast, and number of animals needed for research can be considerably decreased. The contractor will specifically: 1). establish a methodology to obtain a cell culture system(s) that reflect the characteristics of the placental barrier as closely as possible; unequivocally demonstrate that the cell culture system selected is the most relevant to the proposed studies. 2). investigate the nature and levels of enzymes at different gestational periods. 3). perform permeability studies on drugs of abuse and their metabolites 4).perform permeability studies for opioid peptides across the placental barrier model and compare with the permeability and metabolism of the peptides across the blood brain barrier. 5). investigate in vitro drug-drug interaction between drugs used in the treatment of AIDS and drugs of abuse for placental permeability, drug metabolism and enzyme levels. 6). investigate in vitro drug-drug interaction between the drugs for the treatment of tuberculosis and drugs of abuse for placental permeability, drug metabolism, effects on enzyme levels. 7). perform drug interaction studies with other drugs of abuse (such as cocaine and morphine).